Spacecraft are typically designed with a primary focus on weight in order to meet launch vehicle performance parameters. However, for pressurized and/or man-rated spacecraft, it is also necessary to have an understanding of the vehicle operating environments to properly size the pressure vessel. Proper sizing of the pressure vessel requires an understanding of the space vehicle's life cycle and compares the physical design optimization (weight and launch "cost") to downstream operational complexity and total life cycle cost. This paper will provide an overview of some major environmental design drivers and provide examples for calculating the optimal design pressure versus a selected set of design parameters related to thermal and environmental perspectives. In addition, this paper will provide a generic set of cracking pressures for both positive and negative pressure relief valves that encompasses worst case environmental effects for a variety of launch / landing sites. Finally, several examples are included to highlight pressure relief set points and vehicle weight impacts for a selected set of orbital missions.